RESUMO
In this work, the new diaminochromenes: 2,5-dimono-8-methoxychromeno[4,3,2-de][1,6]naphthyridine-4-carbonitrile (4), 8-ethoxy-2-imino-3,4-dihydro-2H-chromene-3-carbonitrile-4-malononitrile (5), 2,5-diamino-8-ethoxychromene[4,3,2-de][1,6]naphthyridine-4-carbonotrile (6), were synthesized and fully characterized through 600 MHz using 1H, 13C, APT, gHSQC, gHMBC, ROESY-1D and gated decoupling 13C. Further docking studies suggested that these compounds are capable of intercalating with the Drew-Dickerson Dodecamer DNA and, therefore, be candidates to work as effective compounds to decrease the cancer radiotherapy.Communicated by Ramaswamy H. Sarma.
Assuntos
Antineoplásicos , Antineoplásicos/farmacologia , DNA , Espectroscopia de Ressonância Magnética , Simulação de Acoplamento MolecularRESUMO
The compounds 7-chloro-9-(2-hydroxy-4,4-dimethyl-6-oxocyclohex-1-en-1-yl)-3,3-dimethyl-2,3,4,9-tetrahydro-1H-xanthen-1-one (5) and 5-[-7-chloro-2,4-dioxo-1H, 2H, 3H, 4H, 5H-chromeno[2,3-d]pyrimidin-5-yl)]-1,3-diazinane-2,4,6-trione (7), were synthesized from dimedone and barbituric acid and had their three-dimensional structures and precise chemical shifts assignments obtained by Nuclear Magnetic Resonance (NMR) from 1H, 13C, APT, COSY, HSQC, and HMBC spectra. Additional HOMO-LUMO DFT calculations corroborated the NMR results and pointed to the most stable stereoisomers of each compound. Besides, further docking and molecular dynamic studies suggest that the stereoisomers (9S)-7-chloro-9-(2-hydroxy-4,4-dimethyl-6-oxocyclohex-1-en-1-yl)-3,3-dimethyl-2,3,4,9-tetrahydro-1H-xanthen-1-one, and 5-[(5S)-7-chloro-2,4-dioxo-1H, 2H, 3H, 4H, 5H-chromeno[2,3-d]pyrimidin-5-yl)]-1,3-diazinane-2,4,6-trione of these compounds may act as DNA intercalators and qualify as potential leads for the development of new anticancer drugs.Communicated by Ramaswamy H. Sarma.